%0 Journal Article
%T Retron-Eco1 assembles NAD+-hydrolyzing filaments that provide immunity against bacteriophages.
%A Carabias A
%A Camara-Wilpert S
%A Mestre MR
%A Lopéz-Méndez B
%A Hendriks IA
%A Zhao R
%A Pape T
%A Fuglsang A
%A Luk SH
%A Nielsen ML
%A Pinilla-Redondo R
%A Montoya G
%J Mol Cell
%V 84
%N 11
%D 2024 Jun 6
%M 38788717
%F 19.328
%R 10.1016/j.molcel.2024.05.001
%X Retrons are toxin-antitoxin systems protecting bacteria against bacteriophages via abortive infection. The Retron-Eco1 antitoxin is formed by a reverse transcriptase (RT) and a non-coding RNA (ncRNA)/multi-copy single-stranded DNA (msDNA) hybrid that neutralizes an uncharacterized toxic effector. Yet, the molecular mechanisms underlying phage defense remain unknown. Here, we show that the N-glycosidase effector, which belongs to the STIR superfamily, hydrolyzes NAD+ during infection. Cryoelectron microscopy (cryo-EM) analysis shows that the msDNA stabilizes a filament that cages the effector in a low-activity state in which ADPr, a NAD+ hydrolysis product, is covalently linked to the catalytic E106 residue. Mutations shortening the msDNA induce filament disassembly and the effector's toxicity, underscoring the msDNA role in immunity. Furthermore, we discovered a phage-encoded Retron-Eco1 inhibitor (U56) that binds ADPr, highlighting the intricate interplay between retron systems and phage evolution. Our work outlines the structural basis of Retron-Eco1 defense, uncovering ADPr's pivotal role in immunity.